Association between BCL2 interacting protein 3 like (BNIP3L) genetic polymorphisms and the risk of multiple myeloma in China.

BACKGROUND: The BCL2 interacting protein 3-like (BNIP3L) protein is involved in multiple myeloma (MM) development and progression. This study aims to explore the connection between BNIP3L single-nucleotide polymorphisms (SNPs) and MM. METHODS: SNaPshot was used to examine six SNP loci of the BNIP3L gene in enrolled subjects. The relationship between these loci and MM susceptibility and prognosis was explored. Survival analysis was used to evaluate the impact of different factors on patient survival. RESULTS: The rs2874670 AA genotype and A allele were associated with increased MM risk (P < 0.05). The CCACAC haplotype had a higher frequency in MM, while CCGCAC had a higher frequency in normal patients (all P < 0.05). Patients with R-ISS stage I and II had higher survival rates than those with stage III (P < 0.05). Patients, who received chemotherapy followed by autologous stem cell transplantation, had longer survival time than those who only received chemotherapy (P < 0.05). Low levels of LDH and ß2-MG were associated with better survival rates (P < 0.05). Cox regression identified that LDH levels, ß2-MG levels, and R-ISS staging were the risk factors for the death of MM. Mann-Whitney U test found a significant difference in survival time between MM patients with different BNIP3L rs2874670 genotypes after BD chemotherapy (P < 0.05). CONCLUSION: To our knowledge, this is the first study to find that BNIP3L rs2874670 could increase MM susceptibility in China. Different BNIP3L rs2874670 genotypes may affect the prognosis of MM patients receiving BD chemotherapy.

Causal association between adiposity and hemorrhoids: a Mendelian randomization study.

Background: Hemorrhoids are a very common anorectal disorder affecting a large number of individuals throughout the world. This study aimed to evaluate the causal effects of four adiposity traits including body mass index (BMI), body fat percentage, waist circumference, and waist-to-hip ratio on hemorrhoids by Mendelian randomization (MR). Methods: We used summary statistics of BMI (N = 461,460), body fat percentage (N = 454,633), waist circumference (N = 462,166), waist-to-hip ratio (N = 212,244), and hemorrhoids (N = 337,199) from large-scale genome wide association studies of European ancestry. Univariable and multivariable MR were carried out to infer causality. The MR Steiger directionality test was used to test the causal direction. Results: The primary MR analysis using the inverse variance weighted (IVW) method showed that there were positive effects of genetically determined BMI [odds ratio (OR) = 1.005, 95% confidence interval (CI): 1.003-1.008, per standard deviation (SD), p = 7.801 × 10-5], body fat percentage (OR = 1.005, 95% CI: 1.001-1.008, per SD, p = 0.008), waist circumference (OR = 1.008, 95% CI: 1.005-1.011, per SD, p = 1.051 × 10-6), and waist-to-hip ratio (OR = 1.010, 95% CI: 1.003-1.017, per SD, p = 0.003) on hemorrhoids. These findings were robust in multivariable MR adjusting for physical activity. The Steiger directionality test showed evidence against reverse causation. Conclusion: Our MR study supports a causal role of adiposity in the development of hemorrhoids. Adiposity prevention may be an important strategy for reducing hemorrhoids risk.

Tiliacora triandra extract and its major constituent attenuates diabetic kidney and testicular impairment by modulating redox imbalance and pro-inflammatory responses in rats.

BACKGROUND: Literature has demonstrated that diabetes is associated with renal complication and testicular dysfunctions. The current study explored the potential of Tiliacora triandra extract and its major component against diabetic kidney and testicular damages in rats. METHODS: Diabetes was induced by high fat diet/streptozotocin (HFD/STZ) and treated orally with Tiliacora triandra extract (TTE, 100 and 400 mg kg-1 body weight) and its major component, 5,7-dihydroxy-6-oxoheptadecanoic acid (DHA, 25 mg kg-1 body weight) for 30 consecutive days. Testicular activities of testicular enzymes, serum levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), sperm parameters and urinalysis for protein and albumin levels were evaluated. Renal and testicular biomarkers of oxidative stress and pro-inflammation were analysed along with histology. RESULTS: The experimental diabetes induced significant alterations in the levels and activities of indices evaluated compared to non-diabetic normal rats. The 28-day treatment of diabetic rats with TTE and DHA markedly improved activities of testicular enzymes, restored levels of testosterone, LH and FSH and sperm parameters compared to untreated diabetic rats. TTE and DHA abrogated proteinuria and reversed urine albumin level. Testicular and renal oxidative stress and pro-inflammation were attenuated in diabetic rats treated with TTE and DHA. The diabetes-mediated histopathological damage was alleviated in the kidney and testis. CONCLUSION: The protective effect of TTE and DHA against diabetes induced kidney and testicular damages may be related to its antioxidant and anti-inflammatory activities. © 2020 Society of Chemical Industry.

lncRNA Erbb4-IR is downregulated in prostate carcinoma and predicts prognosis.

Long non-coding (lnc) RNA Erbb4-IR has been associated with diabetic renal injury; however, its roles in other diseases remain unknown. Therefore, the present study investigated the involvement of Erbb4-IR in prostate carcinoma. Reverse transcription-quantitative PCR was used to analyze gene expression in tissue samples collected from patients with prostate carcinoma. Overexpression experiments via cell transfection were performed to determine the association between Erbb4-IR and microRNA (miR)-21. Furthermore, Cell Counting Kit-8 and cell apoptosis assays were performed to assess cell proliferation and apoptotic rate, respectively. The results revealed that Erbb4-IR was downregulated in prostate carcinoma tissues compared with adjacent non-cancerous tissues, and that low expression of Erbb4-IR in tumor tissues was closely associated with poor survival. Furthermore, miR-21 was upregulated in prostate carcinoma tissues compared with adjacent non-cancerous tissues and was inversely associated with Erbb4-IR expression in tumor tissues. In vitro cell experiments revealed that Erbb4-IR overexpression resulted in the downregulation of miR-21, while miR-21 overexpression did not significantly affect the expression of Erbb4-IR. Moreover, Erbb4-IR overexpression increased apoptosis and inhibited the proliferation of prostate carcinoma cells. miR-21 overexpression resulted in the opposite effect and attenuated the effects of Erbb4-IR overexpression. Therefore, the results of the present study suggested that lncRNA Erbb4-IR is downregulated in prostate carcinoma and may inhibit cancer development by downregulating miR-21.

Genome-Wide Screening for Novel Candidate Virulence Related Response Regulator Genes in Xanthomonas oryzae pv. oryzicola.

Two-component regulatory system (TCS), a major type of cellular signal transduction system, is widely used by bacteria to adapt to different conditions and to colonize certain ecological niches in response to environmental stimuli. TCSs are of distinct functional diversity, genetic diversity, and species specificity (pathovar specificity, even strain specificity) across bacterial groups. Although TCSs have been demonstrated to be crucial to the virulence of Xanthomonas, only a few researches have been reported about the studies of TCSs in Xanthomonas oryzae pathovar oryzicola (hereafter Xoc), the pathogen of rice bacterial streak disease. In the genome of Xoc strain GX01, it has been annotated 110 TCSs genes encoding 54 response regulators (RRs), 36 orthodox histidine kinase (HKs) and 20 hybrid histidine kinase (HyHKs). To evaluate the involvement of TCSs in the stress adaptation and virulence of Xoc, we mutated 50 annotated RR genes in Xoc GX01 by homologous vector integration mutagenesis and assessed their phenotypes in given conditions and tested their virulence on host rice. 17 RR genes were identified to be likely involved in virulence of Xoc, of which 10 RR genes are novel virulence genes in Xanthomonas, including three novel virulence genes for bacteria. Of the novel candidate virulence genes, some of which may be involved in the general stress adaptation, exopolysaccharide production, extracellular protease secretion and swarming motility of Xoc. Our results will facilitate further studies on revealing the biological functions of TCS genes in this phytopathogenic bacterium.